The use of new heat-not-burn electronic cigarettes increase pulmonary oxidative stress, damage DNA and alter ultrastructural lung airways.

Recently, the Food and Drug Administration authorized the Heat not Burn (HnB) IQOS Tobacco Heating System for marketing as Modified Risk Tobacco. However, to date there are no robust evidence of a lower health risk for consumers. The present study was conceived to help fill the knowledge gap on toxicological outcomes associated with IQOS by exploring its effects on lung structure along with its genotoxic and co-carcinogenic potential. Male Sprague-Dawley rats were exposed using a whole-body mode. The puff profile consisted in (5 s on, 15 s off, 5 s on) with an airflow of 4 L/min. The puff profile and flow rate were determined in accordance with previous studies on e-cigarettes. Daily treatments were scheduled for five consecutive days/week followed by two days off, for 4 consecutive weeks. Our results show the presence of irritating and carcinogenic compounds including aldehydes and polycyclic aromatic hydrocarbons in the IQOS mainstream as sign of incomplete combustion and tobacco degradation. We measured the radical species yield (RRS) in lung biopsies by electronic paramagnetic resonance (EPR) using the “spin probe” (bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl) decandioate dihydrochloride). The nitroxide spectra were recorded as marker of RRS detection. We have shown that IQOS smoke increases tissue RRS concentration promoting severe remodeling of smaller and largest rat airways, oxidative DNA breakage damage. IQOS exposure triggered an inflammatory response with higher levels of pro-inflammatory mediators such as TNF-α; CCL3 CSF2 and COX commonly observed in tobacco smoking models. In addition, the exposed animals showed increased expression of the mitogen activated protein kinase stimulating pathway that is involved in cancer progression induced by conventional tobacco smoke. IQOS has been proposed as a safer alternative to conventional cigarettes, due to reduced concentration of various harmful constituents typical of traditional tobacco smoke. However, our findings confirm that IQOS smoke contains byproducts of pyrolysis and thermogenic degradation, the same harmful constituents of traditional cigarette smoke, and for the first time, we demonstrate that it causes grave lung damage and promotes factors that increase the risk of cancer in the animal model.